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Interleukin-15 receptor blockade in non-human primate kidney transplantation.

dc.contributor.author Faure, JP
dc.contributor.author Fechner, J
dc.contributor.author Haustein, S
dc.contributor.author Kayaoglu, A
dc.contributor.author Knechtle, Stuart J
dc.contributor.author Kwun, J
dc.contributor.author Roenneburg, D
dc.contributor.author Torrealba, J
dc.coverage.spatial United States
dc.date.accessioned 2015-05-16T11:59:14Z
dc.date.issued 2010-04-27
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/20134394
dc.identifier.uri https://hdl.handle.net/10161/10064
dc.description.abstract BACKGROUND: Interleukin (IL)-15 is a chemotactic factor to T cells. It induces proliferation and promotes survival of activated T cells. IL-15 receptor blockade in mouse cardiac and islet allotransplant models has led to long-term engraftment and a regulatory T-cell environment. This study investigated the efficacy of IL-15 receptor blockade using Mut-IL-15/Fc in an outbred non-human primate model of renal allotransplantation. METHODS: Male cynomolgus macaque donor-recipient pairs were selected based on ABO typing, major histocompatibility complex class I typing, and carboxy-fluorescein diacetate succinimidyl ester-based mixed lymphocyte responses. Once animals were assigned to one of six treatment groups, they underwent renal transplantation and bilateral native nephrectomy. Serum creatinine level was monitored twice weekly and as indicated, and protocol biopsies were performed. Rejection was defined as a increase in serum creatinine to 1.5 mg/dL or higher and was confirmed histologically. Complete blood counts and flow cytometric analyses were performed periodically posttransplant; pharmacokinetic parameters of Mut-IL-15/Fc were assessed. RESULTS: Compared with control animals, Mut-IL-15/Fc-treated animals did not demonstrate increased graft survival despite adequate serum levels of Mut-IL-15/Fc. Flow cytometric analysis of white blood cell subgroups demonstrated a decrease in CD8 T-cell and natural killer cell numbers, although this did not reach statistical significance. Interestingly, two animals receiving Mut-IL-15/Fc developed infectious complications, but no infection was seen in control animals. Renal pathology varied widely. CONCLUSIONS: Peritransplant IL-15 receptor blockade does not prolong allograft survival in non-human primate renal transplantation; however, it reduces the number of CD8 T cells and natural killer cells in the peripheral blood.
dc.language eng
dc.relation.ispartof Transplantation
dc.relation.isversionof 10.1097/TP.0b013e3181d05a58
dc.subject Animals
dc.subject Antilymphocyte Serum
dc.subject Biomarkers
dc.subject Biopsy
dc.subject CD8-Positive T-Lymphocytes
dc.subject Creatinine
dc.subject Drug Therapy, Combination
dc.subject Flow Cytometry
dc.subject Graft Rejection
dc.subject Graft Survival
dc.subject Humans
dc.subject Immunoglobulin Fc Fragments
dc.subject Immunosuppressive Agents
dc.subject Kidney Transplantation
dc.subject Killer Cells, Natural
dc.subject Lymphocyte Count
dc.subject Macaca fascicularis
dc.subject Male
dc.subject Mice
dc.subject Models, Animal
dc.subject Mycophenolic Acid
dc.subject Receptors, Interleukin-15
dc.subject Time Factors
dc.subject Transplantation, Homologous
dc.title Interleukin-15 receptor blockade in non-human primate kidney transplantation.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/20134394
pubs.begin-page 937
pubs.end-page 944
pubs.issue 8
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Clinical Research Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group School of Medicine
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Abdominal Transplant Surgery
pubs.publication-status Published
pubs.volume 89
dc.identifier.eissn 1534-6080


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